Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “nulling”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,369 records · Page 76
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Knockout of AKAP150 improves impaired BK channel‐mediated vascular dysfunction through the Akt/GSK3β signalling pathway in diabetes mellitus

Abstract Vascular dysfunction resulting from diabetes is an important factor in arteriosclerosis. Previous studies have shown that during hyperglycaemia and diabetes, AKAP150 promotes vascular tone enhancement by intensifying the remodelling of the BK channel. However, the interaction between AKAP150 and the BK channel remains open to discussion. In this study, we investigated the regulation of impaired BK channel‐mediated vascular dysfunction in diabetes mellitus. Using AKAP150 null mice (AKAP150 −/− ) and wild‐type (WT) control mice (C57BL/6J), diabetes was induced by intraperitoneal injection of streptozotocin. We found that knockout of AKAP150 reversed vascular remodelling and fibrosis in mice with diabetes and in AKAP150 −/− diabetic mice. Impaired Akt/GSK3β signalling contributed to decreased BK‐β 1 expression in aortas from diabetic mice, and the silencing of AKAP150 increased Akt phosphorylation and BK‐β 1 expression in MOVAS cells treated with HG medium. The inhibition of Akt activity caused a decrease in BK‐β 1 expression, and treatment with AKAP150 siRNA suppressed GSK3β expression in the nuclei of MOVAS cells treated with HG. Knockout of AKAP150 reverses impaired BK channel‐mediated vascular dysfunction through the Akt/GSK3β signalling pathway in diabetes mellitus.

Zhu, Yan‐Rong↗
DOE OSTI2022

Worldwide phylogeography of rough-toothed dolphins ( Steno bredanensis ) provides evidence for subspecies delimitation

Rough-toothed dolphins (Steno bredanensis) have a global tropical and subtropical distribution with oceanic, neritic, and island-associated populations. Here, to inform conservation and management for this species, we used sequences from the mtDNA control region (n = 360), mitogenomes (n = 19), and six nuclear introns (n = 35) to provide multiple lines of evidence to critically evaluate the potential taxonomic status of rough-toothed dolphins. Using samples from the Pacific, Indian, and Atlantic Oceans, we examined the null hypothesis that rough-toothed dolphins are one panmictic species and the alternate hypothesis of oceanic subspecies. Phylogenetic analyses of mitogenomes revealed a private Atlantic clade sister to a larger cosmopolitan clade including individuals from all tropical and subtropical oceans. We dated the split between the Atlantic clade and the cosmopolitan clade to 890,000 years ago. We determined that Atlantic rough-toothed dolphins could be correctly diagnosed with 98% accuracy with the mtDNA control region and calculated the net nucleotide divergence as 0.02. Population level analyses revealed significant genetic differentiation using mtDNA among most regions, while significant differentiation using nuclear markers occurred only between the Atlantic and the Indian/Pacific regions. Therefore, the oceanic divergence and diagnosability of rough-toothed dolphins in the Atlantic and the Indian/Pacific Oceans meet proposed criteria for recognition as two subspecies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

The flagella of ‘ Candidatus Liberibacter asiaticus’ and its movement in planta

Summary Citrus huanglongbing (HLB) is the most devastating citrus disease worldwide. ‘ Candidatus Liberibacter asiaticus’ (Las) is the most prevalent HLB causal agent that is yet to be cultured. Here, we analysed the flagellar genes of Las and Rhizobiaceae and observed two characteristics unique to the flagellar proteins of Las: (i) a shorter primary structure of the rod capping protein FlgJ than other Rhizobiaceae bacteria and (ii) Las contains only one flagellin‐encoding gene flaA (CLIBASIA_02090), whereas other Rhizobiaceae species carry at least three flagellin‐encoding genes. Only flgJ Atu but not flgJ Las restored the swimming motility of Agrobacterium tumefaciens flgJ mutant. Pull‐down assays demonstrated that FlgJ Las interacts with FlgB but not with FliE. Ectopic expression of flaA Las in A. tumefaciens mutants restored the swimming motility of ∆ flaA mutant and ∆ flaAD mutant, but not that of the null mutant ∆ flaABCD . No flagellum was observed for Las in citrus and dodder. The expression of flagellar genes was higher in psyllids than in planta . In addition, western blotting using flagellin‐specific antibody indicates that Las expresses flagellin protein in psyllids, but not in planta . The flagellar features of Las in planta suggest that Las movement in the phloem is not mediated by flagella. We also characterized the movement of Las after psyllid transmission into young flush. Our data support a model that Las remains inside young flush after psyllid transmission and before the flush matures. The delayed movement of Las out of young flush after psyllid transmission provides opportunities for targeted treatment of young flush for HLB control.

Andrade, Maxuel O.↗
DOE OSTI2025

Crash–and–dash: a new era in tree genome editing

In less than a decade since the first demonstrations of CRISPR genome editing of agronomic genes in several tree species (Zhou et al., 2015; Jia et al., 2016; Ren et al., 2016), this disruptive technology has been deployed for a growing number of traits in both basic and applied research. The precision and efficiency of CRISPR editing allow for the recovery of null mutants in the first generation (Zhou et al., 2015; Elorriaga et al., 2018; Muhr et al., 2018), which is a significant benefit for perennial trees with long generation times. The stability of editing outcomes over multiple years or clonal propagation cycles (Bewg et al., 2022; Chen et al., 2023; Goralogia et al., 2024) is another key advantage since most woody perennials are vegetatively propagated in commercial operations. However, in many countries, gene-edited trees with stably integrated T-DNA face the same regulatory hurdles as traditional transgenics, slowing field trial characterization and the integration of transgenesis with conventional breeding (Boerjan & Strauss, 2024). In an article recently published in New Phytologist, Hoengenaert et al. (2025; doi: 10.1111/nph.20415) demonstrate transgene-free editing in poplar (Populus tremula × alba) that shows promise for wide adoption. The CRISPR-edited, transgene-free canker-resistant citrus (Citrus sinensis) trees (Su et al., 2023) have recently been approved by USDA-APHIS and are exempt from regulation by the US Environmental Protection Agency (EPA) for commercial production. The work by Hoengenaert et al. (2025) suggests a similar path could be followed for purpose-grown plantations for bioenergy, bioproducts, and biomaterials.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Repression of jasmonate signaling by a non‐TIFY JAZ protein in Arabidopsis

Summary JAsmonate ZIM‐domain (JAZ) proteins repress the activity of transcription factors that execute responses to the plant hormone jasmonoyl‐L‐isoleucine (JA‐Ile). The ZIM protein domain recruits the co‐repressors NINJA and TOPLESS to JAZ‐bound transcription factors, and contains a highly conserved TIF[F/Y]XG motif that defines the larger family of TIFY proteins to which JAZs belong. Here, we report that diverse plant species contain genes encoding putative non‐TIFY JAZ proteins, including a previously unrecognized JAZ repressor in Arabidopsis (JAZ13, encoded by At3g22275). JAZ13 is most closely related to JAZ8 and includes divergent EAR, TIFY/ZIM, and Jas motifs. Unlike JAZ8, however, JAZ13 contains a Ser‐rich C‐terminal tail that is a site for phosphorylation. Overexpression of JAZ13 resulted in reduced sensitivity to JA, attenuation of wound‐induced expression of JA‐response genes, and decreased resistance to insect herbivory. JAZ13 interacts with the bHLH transcription factor MYC2 and the co‐repressor TOPLESS but, consistent with the absence of a TIFY motif, neither NINJA nor other JAZs. Analysis of single and higher‐order T‐DNA insertion jaz null mutants provided further evidence that JAZ13 is a repressor JA signaling. Our results demonstrate that proteins outside the TIFY family are functional JAZ repressors and further suggest that this expansion of the JAZ family allows fine‐tuning of JA‐mediated transcriptional responses.

Thireault, Caitlin↗
DOE OSTI2016

Epidermal jasmonate perception is sufficient for all aspects of jasmonate‐mediated male fertility in Arabidopsis

Summary Jasmonate ( JA ) signaling is essential for several environmental responses and reproductive development in many plant species. In Arabidopsis thaliana , the most obvious phenotype of JA biosynthetic and perception mutants is profound sporophytic male sterility characterized by failure of stamen filament elongation, severe delay of anther dehiscence and pollen inviability. The site of action of JA in the context of reproductive development has been discussed, but the ideas have not been tested experimentally. To this end we used targeted expression of a COI 1‐ YFP transgene in the coi1‐1 mutant background. As COI 1 is an essential component of the JA co‐receptor complex, the null coi1‐1 mutant is male sterile due to lack of JA perception. We show that expression of COI 1‐ YFP in the epidermis of the stamen filament and anther in coi1 mutant plants is sufficient to rescue filament elongation, anther dehiscence and pollen viability. In contrast, filament expression alone or expression in the tapetum do not restore dehiscence and pollen viability. These results demonstrate that epidermal JA perception is sufficient for anther function and pollen viability, and suggest the presence of a JA ‐dependent non‐autonomous signal produced in the anther epidermis to synchronize both anther dehiscence and pollen maturation.

Jewell, Jeremy B.↗
DOE OSTI2017

Alteration of cell wall xylan acetylation triggers defense responses that counterbalance the immune deficiencies of plants impaired in the β-subunit of the heterotrimeric G-protein

Arabidopsis heterotrimeric G-protein complex modulates pathogen-associated molecular pattern-triggered immunity (PTI) and disease resistance responses to different types of pathogens. It also plays a role in plant cell wall integrity as mutants impaired in the Gβ- ( agb1-2 ) or Gγ-subunits have an altered wall composition compared with wild-type plants. Here we performed a mutant screen to identify suppressors of agb1-2 ( sgb ) that restore susceptibility to pathogens to wild-type levels. Out of the four sgb mutants ( sgb10–sgb13 ) identified, sgb11 is a new mutant allele of ESKIMO1 ( ESK1 ), which encodes a plant-specific polysaccharide O -acetyltransferase involved in xylan acetylation. Null alleles ( sgb11/esk1-7 ) of ESK1 restore to wild-type levels the enhanced susceptibility of agb1-2 to the necrotrophic fungus Plectosphaerella cucumerina BMM ( PcBMM ), but not to the bacterium Pseudomonas syringae pv. tomato DC3000 or to the oomycete Hyaloperonospora arabidopsidis . The enhanced resistance to PcBMM of the agb1-2 esk1-7 double mutant was not the result of the re-activation of deficient PTI responses in agb1-2 . Alteration of cell wall xylan acetylation caused by ESK1 impairment was accompanied by an enhanced accumulation of abscisic acid, the constitutive expression of genes encoding antibiotic peptides and enzymes involved in the biosynthesis of tryptophan-derived metabolites, and the accumulation of disease resistance-related secondary metabolites and different osmolites. Thus. these esk1 -mediated responses counterbalance the defective PTI and PcBMM susceptibility of agb1-2 plants, and explain the enhanced drought resistance of esk1 plants. These results suggest that a deficient PTI-mediated resistance is partially compensated by the activation of specific cell-wall-triggered immune responses.

pathogen-associated molecular pattern↗
DOE OSTI2018

GreenCut protein CPLD 49 of Chlamydomonas reinhardtii associates with thylakoid membranes and is required for cytochrome b 6 f complex accumulation

Summary The GreenCut encompasses a suite of nucleus‐encoded proteins with orthologs among green lineage organisms (plants, green algae), but that are absent or poorly conserved in non‐photosynthetic/heterotrophic organisms. In Chlamydomonas reinhardtii , CPLD 49 ( C onserved in P lant L ineage and D iatoms 49 ) is an uncharacterized GreenCut protein that is critical for maintaining normal photosynthetic function. We demonstrate that a cpld49 mutant has impaired photoautotrophic growth under high‐light conditions. The mutant exhibits a nearly 90% reduction in the level of the cytochrome b 6 f complex (Cyt b 6 f ), which impacts linear and cyclic electron transport, but does not compromise the ability of the strain to perform state transitions. Furthermore, CPLD 49 strongly associates with thylakoid membranes where it may be part of a membrane protein complex with another GreenCut protein, CPLD 38; a mutant null for CPLD 38 also impacts Cyt b 6 f complex accumulation. We investigated several potential functions of CPLD 49, with some suggested by protein homology. Our findings are congruent with the hypothesis that CPLD 38 and CPLD 49 are part of a novel thylakoid membrane complex that primarily modulates accumulation, but also impacts the activity of the Cyt b 6 f complex. Based on motifs of CPLD 49 and the activities of other CPLD 49‐like proteins, we suggest a role for this putative dehydrogenase in the synthesis of a lipophilic thylakoid membrane molecule or cofactor that influences the assembly and activity of Cyt b 6 f .

Wittkopp, Tyler M.↗
DOE OSTI2020

The N–terminal zinc finger of CELLULOSE SYNTHASE6 is critical in defining its functional properties by determining the level of homodimerization in Arabidopsis

Primary cell wall cellulose is synthesized by the cellulose synthase complex (CSC) containing CELLULOSE SYNTHASE1 (CESA1), CESA3 and one of four CESA6–like proteins in Arabidopsis. It has been proposed that the CESA6–like proteins occupy the same position in the CSC, but their underlying selection mechanism remains unclear. We produced a chimeric CESA5 by replacing its N–terminal zinc finger with its CESA6 counterpart to investigate the consequences for its homodimerization, a crucial step in forming higher–order structures during assembly of the CSC. We found that the mutant phenotypes of prc1–1, a cesa6 null mutant, were rescued by the chimeric CESA5, and became comparable to the wild type (WT) and prc1–1 complemented by WT CESA6 in regard to plant growth, cellulose content, cellulose microfibril organization, CSC dynamics and subcellular localization. Bimolecular fluorescence complementation assays were employed to evaluate pairwise interactions between the N–terminal regions of CESA1, CESA3, CESA5, CESA6 and the chimeric CESA5. We verified that the chimeric CESA5 explicitly interacted with all the other CESA partners, comparable to CESA6, whereas interaction between CESA5 with itself was significantly weaker than that of all other CESA pairs. Furthermore, our findings suggest that the homodimerization of CESA6 through its N–terminal zinc finger is critical in defining its functional properties, and possibly determines its intrinsic roles in facilitating higher–order structures in CSCs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Genetic compensation of triacylglycerol biosynthesis in the green microalga Chlamydomonas reinhardtii

Genetic compensation has been proposed to explain phenotypic differences between gene knockouts and knockdowns in several metazoan and plant model systems. With the rapid development of reverse genetic tools such as CRISPR/Cas9 and RNAi in microalgae, it is increasingly important to assess whether genetic compensation affects the phenotype of engineered algal mutants. While exploring triacylglycerol (TAG) biosynthesis pathways in the model alga Chlamydomonas reinhardtii, it was discovered that knockout of certain genes catalyzing rate-limiting steps of TAG biosynthesis, type-2 diacylglycerol acyltransferase genes (DGTTs), triggered genetic compensation under abiotic stress conditions. Genetic compensation of a DGTT1 null mutation by a related PDAT gene was observed regardless of the strain background or mutagenesis approach, for example, CRISPR/Cas 9 or insertional mutagenesis. However, no compensation was found in the PDAT knockout mutant. The effect of PDAT knockout was evaluated in a Δvtc1 mutant, in which PDAT was upregulated under stress, resulting in a 90% increase in TAG content. Knockout of PDAT in the Δvtc1 background induced a 12.8-fold upregulation of DGTT1 and a 272.3% increase in TAG content in Δvtc1/pdat1 cells, while remaining viable. These data suggest that genetic compensation contributes to the genetic robustness of microalgal TAG biosynthetic pathways, maintaining lipid and redox homeostasis in the knockout mutants under abiotic stress. This work demonstrates examples of genetic compensation in microalgae, implies the physiological relevance of genetic compensation in TAG biosynthesis under stress, and provides guidance for future genetic engineering and mutant characterization efforts.

09 BIOMASS FUELS↗
DOE OSTI2021

REGULATORY TESTING AND POSTTEST ANALYSIS OF THE DPP-3 TYPE B SHIPPING CONTAINER FOR NCT AND HAC TESTS

The safe transportation of radioactive material using appropriately designed and certified transportation packages is important to protect the public and environment. Therefore, a comprehensive and rigorous system of packaging requirements are required. The purpose of this test protocol is to determine the effects of drop testing on package performance in a Type B shipping package (DPP-3). Required physical tests for the DPP-3 package include normal conditions of transport and hypothetical accident conditions test requirements. The preparation, regulatory testing, and post-test evaluation of a Type B shipping package tested to the 10 CFR 71.71 and 10 CFR 71.73 requirements will be presented. Six packages were tested and the responses when subjected to the HAC sequence of free drop, puncture, and thermal tests according to 10 CFR 71.73 were measured. The posttest helium leak test showed a leak rate less than 1 × 10-7 He-cc/sec which means that the containment boundary was maintained after the regulatory testing, therefore maintaining a leak tight environment. To determine the amount of change in the package performance measurements, statistical analyses were conducted using SPSS version 26. The null hypothesis of the testing was that there would not be a change in the measurements from pre to post-testing large enough to find statistical significance. Therefore, a finding of statistical significance indicated too much variability in the package design and was deemed an unfavorable finding. A repeated measures t-test was used to analyze the drum lids and CV torques. A one-way ANOVA was used to analyze height and diameter packages. Results of the repeated measures t-test indicated that all six containment vessel lid torques were statistically significant. However only three out of the six drum lid torques were statistically significant. Therefore, design of the lids caused more variability than necessary when subjected to the following drop tests: 1.) horizontal and cold; 2.) vertical lid down; and 3.) corner with lid up. Results of the one-way ANOVA analysis on height indicated that four out of the six CTUs were statistically significant. Thus, design of the CTUs caused more variability then necessary when subjected to the following drop tests: 1.) horizontal hot; 2.) horizontal cold; 3.) corner lid up; and 4.) corner lid down. Results of the one-way ANOVA analysis on diameter indicated that all six CTUs were statistically significant. Thus, design of the CTUs caused more variability then necessary when subjected to all of the tests. The DPP-3 design has been shown to be an acceptable design for the transport of radioactive materials. However, results of the statistical analysis reveal a possible improvement in package and test design to reduce variability in package performance measurement before and after testing.

Martinez, Oscar↗
DOE OSTI2015

High-accuracy Aspheric X-ray Mirror Metrology Using Software Configurable Optical Test System/deflectometry

The Software Configurable Optical Test System (SCOTS) uses deflectometry to measure surface slopes of general optical shapes without the need for additional null optics. Careful alignment of test geometry and calibration of inherent system error improve the accuracy of SCOTS to a level where it competes with interferometry. We report a SCOTS surface measurement of an off-axis superpolished elliptical x-ray mirror that achieves <1 nm<1 nm root-mean-square accuracy for the surface measurement with low-order term included.

42 ENGINEERING↗
DOE OSTI2024

Binary pseudo-random array for calibration of interferometers with transmission spheres and cylinders

Binary pseudo-random array (BPRA) “white noise” artifacts are highly effective for characterizing the instrument transfer function (ITF) of surface topography metrology tools and wavefront measurement instruments. These BPRA artifacts feature all spatial frequencies within the instrument bandpass equally, resulting in a power spectral density with a white-noise-like character. This characteristic allows for direct ITF determination with uniform sensitivity across the entire spatial frequency range. We have developed a novel BPRA calibration standard that combines the diffractive pattern of a reflection computer-generated hologram (CGH) with the white noise generating BPRA pattern. By integrating these technologies using the same lithographic techniques, the resulting calibration sample enables ITF characterization of a Fizeau interferometer with a transmission sphere, or any nulling optic.

Munechika, K↗
DOE OSTI2013

ROC analysis in patient specific quality assurance

Purpose: This work investigates the use of receiver operating characteristic (ROC) methods in patient specific IMRT quality assurance (QA) in order to determine unbiased methods to set threshold criteria for {gamma}-distance to agreement measurements. Methods: A group of 17 prostate plans was delivered as planned while a second group of 17 prostate plans was modified with the introduction of random multileaf collimator (MLC) position errors that are normally distributed with {sigma}{approx}{+-}0.5, {+-}1.0, {+-}2.0, and {+-}3.0 mm (a total of 68 modified plans were created). All plans were evaluated using five different {gamma}-criteria. ROC methodology was applied by quantifying the fraction of modified plans reported as 'fail' and unmodified plans reported as 'pass.'Results: {gamma}-based criteria were able to attain nearly 100% sensitivity/specificity in the detection of large random errors ({sigma} > 3 mm). Sensitivity and specificity decrease rapidly for all {gamma}-criteria as the size of error to be detected decreases below 2 mm. Predictive power is null with all criteria used in the detection of small MLC errors ({sigma} < 0.5 mm). Optimal threshold values were established by determining which criteria maximized sensitivity and specificity. For 3%/3 mm {gamma}-criteria, optimal threshold values range from 92% to 99%, whereas for 2%/2 mm, the range was from 77% to 94%. Conclusions: The optimal threshold values that were determined represent a maximized test sensitivity and specificity and are not subject to any user bias. When applied to the datasets that we studied, our results suggest the use of patient specific QA as a safety tool that can effectively prevent large errors (e.g., {sigma} > 3 mm) as opposed to a tool to improve the quality of IMRT delivery.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-I-67: Arachnoid Cysts: The Role of the BLADE Technique

Purpose: The purpose of this study is first to show the extent by which BLADE sequences can reduce all the image artifacts and second to verify that the usefulness of this technique in certain pathological conditions is significant. Methods: In this study, fourteen consecutive patients (5 females, 9 males), who routinely underwent MRI brain examination, between 2010–2014, were selected. The applied routine protocols for brain MR examination included the following sequences: 1) T2-W FLAIR axial; 2) T2-W TSE axial; 3) T2*-W axial, 4) T1-W TSE sagittal; 5) DWI-W axial; 6) T1-W TSE axial; 7) T1-W TSE axial+contrast. In cases of cystic tumors, the T2-W FLAIR BLADE sequence was added to the protocol. All the images were evaluated independently at two separate settings with 3 weeks interval by two radiologists. The radiologists also evaluated the presence of image artifacts (motion, flow, chemical shift, Gibbs ringing). To evaluate the size of the cyst, the two radiologists compared the two techniques (conventional and BLADE) by assessing the extent of the divergence in the measurements of the cysts. Results: Regarding the extent of the cyst size, BLADE measurements were found to be more reliable than the conventional ones with the differences being statistically significant (p<0.01). The qualitative measurements indicated that the T2 FLAIR BLADE sequences were superior to the conventional T2 FLAIR with statistically significant differences (p<0.001) in the following characteristics: 1) overall image quality, 2) CSF nulling; 3) contrast at the pathology and its surrounding; 4) limits of the pathology; 5) motion artifacts; 6) flow artifacts; 7) chemical shift artifacts and 8) Gibbs ringing artifacts. Conclusion: BLADE sequence was found to decrease both flow artifacts in the temporal lobes and motion artifacts from the orbits and it is proposed for clinical use.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-T-642: PTV Is the Voxel-Wise Worst-Case of CTV in Prostate Photon Therapy

Purpose: To examine the adequacy of the planning target volume (PTV) dose distribution as the worst-case representation of clinical target volume (CTV) dose distribution in prostate volumetric-modulated arc therapy (VMAT) plans. Methods: Ten intact prostate cancer cases treated by VMAT at our institution were randomly selected. Isocenter was shifted in the three cardinal directions by a displacement equal to the PTV expansion on the CTV (±3 mm) for a total of six shifted plans per original plan. Rotationally-perturbed plans were generated with a couch rotation of ±1° to simulate patient yaw. The eight perturbed dose distributions were recalculated in the treatment planning system using the same, fixed fluence map as the original plan. The voxel-wise worst-case CTV dose distribution was constructed from the minimum value per voxel from the eight perturbed doses. The resulting dose volume histograms (DVH) were evaluated for statistical correlation between the worst-case CTV and nominal PTV dose distributions based on D95% by Wilcoxon signed-rank test with significance level p ≤ 0.05. Results: Inspection demonstrates the PTV DVH in the nominal dose distribution is bounded by the CTV DVH in the worst-case dose distribution. Comparison of D95% for the two dose distributions by Wilcoxon signed-rank test gives p = 0.131. Therefore the null hypothesis cannot be rejected since the difference in median values is not statistically significant. Conclusion: The assumption that the nominal dose distribution for PTV represents the worst-case dose distribution for CTV appears valid for the ten plans under examination. Although the worst-case dose distribution is unphysical since the dose per voxel is chosen independently, it serves as a lower bound for the possible CTV coverage. Furthermore, this is consistent with the unphysical nature of the PTV. Minor discrepancies between the two dose distributions are expected since the dose cloud is not strictly static. Funding Support: NIH/NCI K25CA168984, Eagles Cancer Research Career Development, The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, Mayo ASU Seed Grant, and The Kemper Marley Foundation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

SU-E-T-769: T-Test Based Prior Error Estimate and Stopping Criterion for Monte Carlo Dose Calculation in Proton Therapy

Purpose: The Monte Carlo (MC) method is a gold standard for dose calculation in radiotherapy. However, it is not a priori clear how many particles need to be simulated to achieve a given dose accuracy. Prior error estimate and stopping criterion are not well established for MC. This work aims to fill this gap. Methods: Due to the statistical nature of MC, our approach is based on one-sample t-test. We design the prior error estimate method based on the t-test, and then use this t-test based error estimate for developing a simulation stopping criterion. The three major components are as follows.First, the source particles are randomized in energy, space and angle, so that the dose deposition from a particle to the voxel is independent and identically distributed (i.i.d.).Second, a sample under consideration in the t-test is the mean value of dose deposition to the voxel by sufficiently large number of source particles. Then according to central limit theorem, the sample as the mean value of i.i.d. variables is normally distributed with the expectation equal to the true deposited dose.Third, the t-test is performed with the null hypothesis that the difference between sample expectation (the same as true deposited dose) and on-the-fly calculated mean sample dose from MC is larger than a given error threshold, in addition to which users have the freedom to specify confidence probability and region of interest in the t-test based stopping criterion. Results: The method is validated for proton dose calculation. The difference between the MC Result based on the t-test prior error estimate and the statistical Result by repeating numerous MC simulations is within 1%. Conclusion: The t-test based prior error estimate and stopping criterion are developed for MC and validated for proton dose calculation. Xiang Hong and Hao Gao were partially supported by the NSFC (#11405105), the 973 Program (#2015CB856000) and the Shanghai Pujiang Talent Program (#14PJ1404500)

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-F-BRD-06: Robust Dose Calculation in Intensity Modulated Proton Therapy

Purpose: Commissioning data for intensity modulated proton therapy (IMPT) must be post-processed by fits to ad-hoc functions to derive the dose calculation kernel parameters in a treatment planning system (TPS). Whether from experimental measurement or Monte Carlo simulation, the limited and noisy nature of such data makes this task very challenging. We present a method to improve the modeling of the lateral dose distribution of clinical energy proton beams in water to commission an in-house IMPT dose calculation engine. Methods: A linear sum of three Gaussian distribution functions was fitted to the lateral dose data in logarithmic scale. Starting values of fitting solutions were determined from the Generalized Highland Approximation. We exhaustively optimized the combinations of data weights with upper bounds of the fitting solutions to minimize confidence intervals of the fitting solutions while maintaining the coefficient of determination (R{sup 2}). Results: Across all energies, average confidence bounds improved 72.88% [Max: 88.28%, Min: 55.05%] for small angle coulomb scattering, 114.25% [409.13%, 66.72%,] for nuclear scattering, and 68.66% [141.09%, 33.27%] for large angle coulomb scattering, while the coefficients of determination of the fits (R{sup 2}) remained comparable. On average R {sup 2} only changed 0.18% and were very close to 1 (approx. 0.999). Wilcoxon signed rank tests comparing unweighted/unbounded fits with weighted/bounded fits averaged 0.0146 (Max: 0.177, Min: 7.05×10−{sup 7}) for small angle Coulomb, 0.0903 (0.945, 7.05×10−{sup 7}) for nuclear, and 0.254 (0.871, 1.86×10−{sup 6}) for large angle Coulomb scattering. This allows rejection of the null hypothesis for small angle Coulomb scattering at the 0.015 level and nuclear interaction at the 0.1 level. Conclusion: Optimal weights assigned to IMPT lateral dose data minimized fitting to stochastic noise in the tail region. Optimizing the upper bounds of fitting parameters improved the robustness of fitting solutions. Both led to a more physically meaningful dose calculation kernel for the TPS. NIH/NCI K25CA168984, Eagles Cancer Research Career Development, The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, Mayo ASU Seed Grant, and The Kemper Marley Foundation.

60 APPLIED LIFE SCIENCES↗